Gut Microbiota Disruption in Hematologic Cancer Therapy: Molecular Insights and Implications for Treatment Efficacy.

Hematologic malignancies (HMs), including leukemia, lymphoma, and multiple myeloma, involve the uncontrolled proliferation of abnormal blood cells, posing significant clinical challenges due to their heterogeneity and varied treatment responses. Despite recent advancements in therapies that have improved survival rates, particularly in chronic lymphocytic leukemia and acute lymphoblastic leukemia, treatments like chemotherapy and stem cell transplantation often disrupt gut microbiota, which can negatively impact treatment outcomes and increase infection risks. This review explores the complex, bidirectional interactions between gut microbiota and cancer treatments in patients with HMs. Gut microbiota can influence drug metabolism through mechanisms such as the production of enzymes like bacterial ß-glucuronidases, which can alter drug efficacy and toxicity. Moreover, microbial metabolites like short-chain fatty acids can modulate the host immune response, enhancing treatment effectiveness. However, therapy often reduces the diversity of beneficial bacteria, such as Bifidobacterium and Faecalibacterium, while increasing pathogenic bacteria like Enterococcus and Escherichia coli. These findings highlight the critical need to preserve microbiota diversity during treatment. Future research should focus on personalized microbiome-based therapies, including probiotics, prebiotics, and fecal microbiota transplantation, to improve outcomes and quality of life for patients with hematologic malignancies.

Exploring Atrial Fibrillation: Understanding the Complex Relation Between Lifestyle and Genetic Factors.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide across diverse ethnic groups. Among these, atrial fibrillation (AF) stands as one of the most prevalent types of arrhythmias and the primary cause of stroke. Risk factors associated with AF include alcohol consumption, aging, high blood pressure, hypertension, inflammation, and genetic factors. A family history of CVD could indicate an increased risk. Consequently, genetic, and genomic testing should be performed to identify the molecular etiology of CVDs and assess at-risk patients. It is important to note that CVDs are the results of the complex interplay of genes and environmental factors, including ethnicity. In this case, the proband's clinic story includes a history of smoking abuse for 10 years (10 cigarettes per day), obesity, hypertension, and an associated familial history. These risk factors, along with genetic variants, could trigger the early onset of AF. In recent years, genetic and genomic studies have significantly advanced our understanding of CVD etiology, given that next-generation sequencing (NGS) allows for the identification of genetic variants that could contribute to these pathologies. Furthermore, NGS facilitates early diagnosis, personalized pharmacological approaches, and identification of novel biomarkers. Thus, NGS is a valuable tool in CVD management. However, such studies are limited in Ecuador, a low- and middle-income country. Several challenges contribute to this gap, encompassing economic, infrastructural, and educational obstacles. Notably, the cost of genetic and genomic studies may also pose a barrier, restricting access to a portion of the population. In this case report, we present a 56-year-old Ecuadorian woman, who has been diagnosed with AF; however, after performing NGS no disease-associated variants were found, despite having strong clinical signs and symptoms. In summary, this case report contributes valuable insights into the complex interplay between genetic and lifestyle factors in the development and management of AF. The case report aims to underscore the potential impact of genetic variants on disease risk, even when classified as variants of uncertain significance, and the importance of an integral approach to patient care that includes genetic screening, lifestyle interventions, and tailored pharmacological treatment.

Assessment of the COVID-19 pandemic progression in Ecuador through seroprevalence analysis of anti-SARS-CoV-2 IgG/IgM antibodies in blood donors.

Introduction: Coronavirus Disease 2019 (COVID-19) is a severe respiratory illness caused by the RNA virus SARS-CoV-2. Globally, there have been over 759.4 million cases and 6.74 million deaths, while Ecuador has reported more than 1.06 million cases and 35.9 thousand deaths. To describe the COVID-19 pandemic impact and the vaccinations effectiveness in a low-income country like Ecuador, we aim to assess the seroprevalence of IgG and IgM antibodies against SARS-CoV-2 in a sample from healthy blood donors at the Cruz Roja Ecuatoriana. Methods: The present seroprevalence study used a lateral flow immunoassay (LFIA) to detect anti-SARS-CoV-2 IgG and IgM antibodies in months with the highest confirmed case rates (May 2020; January, April 2021; January, February, June, July 2022) and months with the highest vaccination rates (May, June, July, August, December 2021) in Quito, Ecuador. The IgG and IgM seroprevalence were also assessed based on sex, age range, blood type and RhD antigen type. The sample size was 8,159, and sampling was performed based on the availability of each blood type. Results: The results showed an overall IgG and IgM seroprevalence of 47.76% and 3.44%, respectively. There were no differences in IgG and IgM seroprevalences between blood groups and sex, whereas statistical differences were found based on months, age range groups, and RhD antigen type. For instance, the highest IgG seroprevalence was observed in February 2022 and within the 17-26 years age range group, while the highest IgM seroprevalence was in April 2021 and within the 47-56 years age range group. Lastly, only IgG seroprevalence was higher in RhD+ individuals while IgM seroprevalence was similar across RhD types. Discussion: This project contributes to limited data on IgG and IgM antibodies against SARS-CoV-2 in Ecuador. It suggests that herd immunity may have been achieved in the last evaluated months, and highlights a potential link between the RhD antigen type and COVID-19 susceptibility. These findings have implications for public health strategies and vaccine distribution not only in Ecuador but also in regions with similar characteristics.

Identifying genomic variant associated with long QT syndrome type 2 in an ecuadorian mestizo individual: a case report.

Introduction: Long QT syndrome (LQTS) is an autosomal dominant inherited cardiac condition characterized by a QT interval prolongation and risk of sudden death. There are 17 subtypes of this syndrome associated with genetic variants in 11 genes. The second most common is type 2, caused by a mutation in the KCNH2 gene, which is part of the potassium channel and influences the final repolarization of the ventricular action potential. This case report presents an Ecuadorian teen with congenital Long QT Syndrome type 2 (OMIM ID: 613688), from a family without cardiac diseases or sudden cardiac death backgrounds. Case presentation: A 14-year-old girl with syncope, normal echocardiogram, and an irregular electrocardiogram was diagnosed with LQTS. Moreover, by performing Next-Generation Sequencing, a pathogenic variant in the KCNH2 gene p.(Ala614Val) (ClinVar ID: VCV000029777.14) associated with LQTS type 2, and two variants of uncertain significance in the AKAP9 p.(Arg1654GlyfsTer23) (rs779447911), and TTN p. (Arg34653Cys) (ClinVar ID: VCV001475968.4) genes were identified. Furthermore, ancestry analysis showed a mainly Native American proportion. Conclusion: Based on the genomic results, the patient was identified to have a high-risk profile, and an implantable cardioverter defibrillator was selected as the best treatment option, highlighting the importance of including both the clinical and genomics aspects for an integral diagnosis.

Genomic analysis of an Ecuadorian individual carrying an SCN5A rare variant.

BACKGROUND: Ion channels, vital transmembrane protein complexes, regulate ion movement within cells. Germline variants in channel-encoding genes lead to channelopathies. The sodium channels in cardiac cells exhibit a structure of an alpha subunit and one to two beta subunits. The alpha subunit, encoded by the SCN5A gene, comprises four domains. CASE PRESENTATION: A fifteen-year-old Ecuadorian female with atrial flutter and abnormal sinus rhythm with no familial history of cardiovascular disease underwent NGS with the TruSight Cardio kit (Illumina). A likely pathogenic SCN5A gene variant (NM_188056.2:c.2677 C > Tp. Arg893Cys) was identified, associated with arrhythmias, long QT, atrial fibrillation, and Brugada syndrome. Ancestral analysis revealed a predominant European component (43.9%), followed by Native American (35.7%) and African (20.4%) components. CONCLUSIONS: The participant presents atrial flutter and conduction disorders, despite lacking typical cardiovascular risk factors. The proband carries a SCN5A variant that has not been previously reported in Latin America and may be associated to her phenotype. The documented arginine-to-cysteine substitution at position 893 in the protein is crucial for various cellular functions. The subject's mixed genetic composition highlights potential genetic contributors to atrial flutter, emphasizing the need for comprehensive genetic studies, particularly in mixed populations like Ecuadorians. This case underscores the importance of genetic analysis for personalized treatment and the significance of studying diverse genetic backgrounds in understanding cardiovascular diseases.

Impact of fundamental components of the Mediterranean diet on the microbiota composition in blood pressure regulation.

BACKGROUND: The Mediterranean diet (MedDiet) is a widely studied dietary pattern reflecting the culinary traditions of Mediterranean regions. High adherence to MedDiet correlates with reduced blood pressure and lower cardiovascular disease (CVD) incidence and mortality. Furthermore, microbiota, influenced by diet, plays a crucial role in cardiovascular health, and dysbiosis in CVD patients suggests the possible beneficial effects of microbiota modulation on blood pressure. The MedDiet, rich in fiber and polyphenols, shapes a distinct microbiota, associated with higher biodiversity and positive health effects. The review aims to describe how various Mediterranean diet components impact gut microbiota, influencing blood pressure dynamics. MAIN BODY: The MedDiet promotes gut health and blood pressure regulation through its various components. For instance, whole grains promote a healthy gut microbiota given that they act as substrates leading to the production of short-chain fatty acids (SCFAs) that can modulate the immune response, preserve gut barrier integrity, and regulate energy metabolism. Other components of the MedDiet, including olive oil, fuits, vegetables, red wine, fish, and lean proteins, have also been associated with blood pressure and gut microbiota regulation. CONCLUSION: The MedDiet is a dietary approach that offers several health benefits in terms of cardiovascular disease management and its associated risk factors, including hypertension. Furthermore, the intake of MedDiet components promote a favorable gut microbiota environment, which, in turn, has been shown that aids in other physiological processes like blood pressure regulation.

The effect of intermittent fasting on microbiota as a therapeutic approach in obesity.

Obesity, a public health challenge, arises from a complex interplay of factors such as dietary habits and genetic predisposition. Alterations in gut microbiota, characterized by an imbalance between Firmicutes and Bacteroidetes, further exacerbate metabolic dysregulation, promoting inflammation and metabolic disturbances. Intermittent fasting (IF) emerges as a promising dietary strategy showing efficacy in weight management and favoring fat utilization. Studies have used mice as animal models to demonstrate the impact of IF on gut microbiota composition, highlighting enhanced metabolism and reduced inflammation. In humans, preliminary evidence suggests that IF promotes a healthy microbiota profile, with increased richness and abundance of beneficial bacterial strains like Lactobacillus and Akkermansia. However, further clinical trials are necessary to validate these findings and elucidate the long-term effects of IF on microbiota and obesity. Future research should focus on specific tissues and cells, the use of advanced -omics techniques, and exploring the interaction of IF with other dietary patterns, to analyze microbiota composition, gene expression, and potential synergistic effects for enhanced metabolic health. While preliminary evidence supports the potential benefits of IF in obesity management and microbiota regulation, further research with diverse populations and robust methodologies is necessary to understand its implications and optimize personalized dietary interventions. This review explores the potential impact of IF on gut microbiota and its intricate relationship with obesity. Specifically, we will focus on elucidating the underlying mechanisms through which IF affects microbiota composition, as well as its subsequent effects on obesity.

Molecular mechanisms of semaglutide and liraglutide as a therapeutic option for obesity.

Obesity, a chronic global health problem, is associated with an increase in various comorbidities, such as cardiovascular disease, type 2 diabetes mellitus, hypertension, and certain types of cancer. The increasing global prevalence of obesity requires research into new therapeutic strategies. Glucagon-like peptide-1 receptor agonists, specifically semaglutide and liraglutide, designed for type 2 diabetes mellitus treatment, have been explored as drugs for the treatment of obesity. This minireview describes the molecular mechanisms of semaglutide and liraglutide in different metabolic pathways, and its mechanism of action in processes such as appetite regulation, insulin secretion, glucose homeostasis, energy expenditure, and lipid metabolism. Finally, several clinical trial outcomes are described to show the safety and efficacy of these drugs in obesity management.

Microbiota dynamics preceding bariatric surgery as obesity treatment: a comprehensive review.

The review present data on the intricate relationship between bariatric surgery, gut microbiota, and metabolic health in obesity treatment. Bariatric surgery, is recognized as an effective intervention for managing morbid obesity, including various techniques with distinct mechanisms of action, efficacy, and safety profiles including Roux-en-Y Gastric Bypass (RYGB), Sleeve Gastrectomy (SG), Laparoscopic Adjustable Gastric Banding (LAGB), and Biliopancreatic Diversion (BPD). RYGB and SG are the most prevalent procedures globally, inducing gut microbiota changes that influence microbial diversity and abundance. Post-surgery, alterations in bacterial communities occur, such as the increased of Escherichia coli inversely correlated with fat mass and leptin levels. During digestion, microbiota produce physiologically active compounds like bile acids (Bas) and short-chain fatty acids (SCFAs). SCFAs, derived by microbial fermentation, influence appetite, energy metabolism, and obesity-related pathways. Bas, altered by surgery, modulate glucose metabolism and insulin sensitivity. Furthermore, SG and RYGB enhance incretin secretion, particularly glucagon-like peptide 1 (GLP-1). Therefore, understanding microbiota changes after bariatric surgery could be crucial for predicting metabolic outcomes and developing targeted interventions for obesity management.

Thyroid cancer in Ecuador: A genetic variants review and a cross-sectional population-based analysis before and after COVID-19 pandemic.

Objectives: The purpose of this study is to describe the genetic variants present in the Ecuadorian population and the incidence and mortality patterns of thyroid cancer in Ecuador from 2016 to 2021. Methods: The present research constitutes a nationwide cross-sectional study encompassing all reported cases of thyroid cancer (C-73) in Ecuador from 2016 to 2021. Incidence rates were calculated based on the annual population at risk, considering factors such as ethnicity, sex, age group, and the geographic location of the incidence. All data was collected from the Hospital Discharge Statistics and the Statistical Registry of General Deaths Databases. Results: Between 2016 and 2021, a total of 20,297 hospital admissions and 921 deaths attributed to thyroid cancer were reported in Ecuador. The incidence of thyroid cancer remained relatively stable from 2016 to 2019. However, there was a notable decrease in 2020, followed by an increase in 2021. Notably, thyroid cancer prevalence rates were found to be higher in highlands regions. Moreover, two genetic variants, the BRAFV600E and KITL678F, have been identified in the Ecuadorian population. It is noteworthy that women exhibited a higher susceptibility to thyroid cancer, being five times more likely than men to develop this condition. Conclusion: Ecuador exhibits one of the highest global incidences of thyroid cancer. Consequently, describing the genetic variants and epidemiological characteristics of thyroid cancer is imperative for enhancing healthcare access and formulating evidence-based public health policies. This research contributes towards a comprehensive understanding of thyroid cancer in the Ecuadorian context, aiming to improve targeted interventions and health outcomes.

Associations of MYPN, TTN, SCN5A, MYO6 and ELN Mutations With Arrhythmias and Subsequent Sudden Cardiac Death: A Case Report of an Ecuadorian Individual.

Cardiac pathologies are among the most frequent causes of death worldwide. Regarding cardiovascular deaths, it is estimated that 5 million cases are caused by sudden cardiac death (SCD) annually. The primary cause of SCD is ventricular arrhythmias. Genomic studies have provided pathogenic, likely pathogenic, and variants of uncertain significance that may predispose individuals to cardiac causes of sudden death. In this study, we describe the case of a 43-year-old individual who experienced an episode of aborted SCD. An implantable cardioverter defibrillator was placed to prevent further SCD episodes. The diagnosis was ventricular fibrillation. Genomic analysis revealed some variants in the MYPN (pathogenic), GCKR (likely pathogenic), TTN (variant of uncertain significance), SCN5A (variant of uncertain significance), MYO6 (variant of uncertain significance), and ELN (variant of uncertain significance) genes, which could be associated with SCD episodes. In addition, a protein-protein interaction network was obtained, with proteins related to ventricular arrhythmia and the biological processes involved. Therefore, this study identified genetic variants that may be associated with and trigger SCD in the individual. Moreover, genetic variants of uncertain significance, which have not been reported, could contribute to the genetic basis of the disease.

Genetic diet interactions of ACE: the increased hypertension predisposition in the Latin American population.

Hypertension is one of the primary risk factors associated with cardiovascular diseases (CVDs). It is a condition that affects people worldwide, and its prevalence is increasing due to several factors, such as lack of physical activity, population aging, and unhealthy diets. Notably, this increase has primarily occurred in low and middle-income countries (LMICs). In Latin America, approximately 40% of adults have been diagnosed with hypertension. Moreover, reports have shown that the Latin American genetic composition is highly diverse, and this genetic background can influence various biological processes, including disease predisposition and treatment effectiveness. Research has shown that Western dietary patterns, which include increased consumption of red meat, refined grains, sugar, and ultra-processed food, have spread across the globe, including Latin America, due to globalization processes. Furthermore, a higher than recommended sodium consumption, which has been associated with hypertension, has been identified across different regions, including Asia, Europe, America, Oceania, and Africa. In conclusion, hypertension is a multifactorial disease involving environmental and genetic factors. In Latin America, hypertension prevalence is increasing due to various factors, including age, the adoption of a "Westernized" diet, and potential genetic predisposition factors involving the ACE gene. Furthermore, identifying the genetic and molecular mechanisms of the disease, its association with diet, and how they interact is essential for the development of personalized treatments to increase its efficacy and reduce side effects.

The Autosomal Short Tandem Repeat Polymorphisms Are Potentially Associated with Cardiovascular Disease Predisposition in the Latin American Population: A Mini Review.

According to the World Health Organization, cardiovascular diseases (CVDs) are the leading cause of death worldwide across nearly all ethnic groups. Inherited cardiac conditions comprise a wide spectrum of diseases that affect the heart, including abnormal structural features and functional impairments. In Latin America, CVDs are the leading cause of death within the region. Factors such as population aging, unhealthy diet, obesity, smoking, and a sedentary lifestyle have increased the risk of CVD. The Latin American population is characterized by its diverse ethnic composition with varying percentages of each ancestral component (African, European, and Native American ancestry). Short tandem repeats (STRs) are DNA sequences with 2-6 base pair repetitions and constitute ~3% of the human genome. Importantly, significant allele frequency variations exist between different populations. While studies have described that STRs are in noncoding regions of the DNA, increasing evidence suggests that simple sequence repeat variations may be critical for proper gene activity and regulation. Furthermore, several STRs have been identified as potential disease predisposition markers. The present review is aimed at comparing and describing the frequencies of autosomal STR polymorphisms potentially associated with cardiovascular disease predisposition in Latin America compared with other populations.

Molecular pathways and nutrigenomic review of insulin resistance development in gestational diabetes mellitus.

Gestational diabetes mellitus is a condition marked by raised blood sugar levels and insulin resistance that usually occurs during the second or third trimester of pregnancy. According to the World Health Organization, hyperglycemia affects 16.9% of pregnancies worldwide. Dietary changes are the primarily alternative treatment for gestational diabetes mellitus. This paper aims to perform an exhaustive overview of the interaction between diet, gene expression, and the metabolic pathways related to insulin resistance. The intake of foods rich in carbohydrates can influence the gene expression of glycolysis, as well as foods rich in fat, can disrupt the beta-oxidation and ketogenesis pathways. Furthermore, vitamins and minerals are related to inflammatory processes regulated by the TLR4/NF-κB and one carbon metabolic pathways. We indicate that diet regulated gene expression of PPARα, NOS, CREB3L3, IRS, and CPT I, altering cellular physiological mechanisms and thus increasing or decreasing the risk of gestational diabetes. The alteration of gene expression can cause inflammation, inhibition of fatty acid transport, or on the contrary help in the modulation of ketogenesis, improve insulin sensitivity, attenuate the effects of glucotoxicity, and others. Therefore, it is critical to comprehend the metabolic changes of pregnant women with gestational diabetes mellitus, to determine nutrients that help in the prevention and treatment of insulin resistance and its long-term consequences.

Role of the gut microbiota in hematologic cancer.

Hematologic neoplasms represent 6.5% of all cancers worldwide. They are characterized by the uncontrolled growth of hematopoietic and lymphoid cells and a decreased immune system efficacy. Pathological conditions in hematologic cancer could disrupt the balance of the gut microbiota, potentially promoting the proliferation of opportunistic pathogens. In this review, we highlight studies that analyzed and described the role of gut microbiota in different types of hematologic diseases. For instance, myeloma is often associated with Pseudomonas aeruginosa and Clostridium leptum, while in leukemias, Streptococcus is the most common genus, and Lachnospiraceae and Ruminococcaceae are less prevalent. Lymphoma exhibits a moderate reduction in microbiota diversity. Moreover, certain factors such as delivery mode, diet, and other environmental factors can alter the diversity of the microbiota, leading to dysbiosis. This dysbiosis may inhibit the immune response and increase susceptibility to cancer. A comprehensive analysis of microbiota-cancer interactions may be useful for disease management and provide valuable information on host-microbiota dynamics, as well as the possible use of microbiota as a distinguishable marker for cancer progression.

The Molecular Mechanisms of the Relationship between Insulin Resistance and Parkinson's Disease Pathogenesis.

Parkinson's disease (PD) is a degenerative condition resulting from the loss of dopaminergic neurons. This neuronal loss leads to motor and non-motor neurological symptoms. Most PD cases are idiopathic, and no cure is available. Recently, it has been proposed that insulin resistance (IR) could be a central factor in PD development. IR has been associated with PD neuropathological features like α-synuclein aggregation, dopaminergic neuronal loss, neuroinflammation, mitochondrial dysfunction, and autophagy. These features are related to impaired neurological metabolism, neuronal death, and the aggravation of PD symptoms. Moreover, pharmacological options that involve insulin signaling improvement and dopaminergic and non-dopaminergic strategies have been under development. These drugs could prevent the metabolic pathways involved in neuronal damage. All these approaches could improve PD outcomes. Also, new biomarker identification may allow for an earlier PD diagnosis in high-risk individuals. This review describes the main pathways implicated in PD development involving IR. Also, it presents several therapeutic options that are directed at insulin signaling improvement and could be used in PD treatment. The understanding of IR molecular mechanisms involved in neurodegenerative development could enhance PD therapeutic options and diagnosis.

The Impact of a Very-Low-Calorie Ketogenic Diet in the Gut Microbiota Composition in Obesity.

The very-low-calorie KD (VLCKD) is characterized by a caloric intake of under 800 kcal/day divided into less than 50 g/day of carbohydrate (13%) and 1 to 1.5 g of protein/kg of body weight (44%) and 43% of fat. This low carbohydrate intake changes the energy source from glucose to ketone bodies. Moreover, clinical trials have consistently shown a beneficial effect of VLCKD in several diseases, such as heart failure, schizophrenia, multiple sclerosis, Parkinson's, and obesity, among others. The gut microbiota has been associated with the metabolic conditions of a person and is regulated by diet interactions; furthermore, it has been shown that the microbiota has a role in body weight homeostasis by regulating metabolism, appetite, and energy. Currently, there is increasing evidence of an association between gut microbiota dysbiosis and the pathophysiology of obesity. In addition, the molecular pathways, the role of metabolites, and how microbiota modulation could be beneficial remain unclear, and more research is needed. The objective of the present article is to contribute with an overview of the impact that VLCKD has on the intestinal microbiota composition of individuals with obesity through a literature review describing the latest research regarding the topic and highlighting which bacteria phyla are associated with obesity and VLCKD.

Identification of mutations on the EMD and EYA4 genes associated with Emery-Dreifuss muscular dystrophy and deafness: a case report.

Introduction: Hearing loss is the most common sensory disability, and it is estimated that 50% of cases are caused by genetic factors. One of the genes associated with deafness is the eyes absent homolog 4 (EYA4) gene, a transcription factor related to the development and function of the inner ear. Emery-Dreifuss muscular dystrophy is a rare inherited disease characterized by atrophy and weakness of the humeroperoneal muscles, multi-joint contractures, and cardiac manifestations. It is inherited in an autosomal-dominant, X-linked, or less frequently autosomal recessive manner; one of the genes associated with EDMD is the emerin (EMD) gene. Case description: A total of two Ecuadorian siblings aged 57 (Subject A) and 55 (Subject B) were diagnosed with deafness and an unspecified type of muscular dystrophy based on family history and clinical findings. Next-generation sequencing (NGS) using the TruSight Cardio and Inherited Disease kits at the Centro de Investigación Genética y Genómica CIGG, Universidad UTE, was performed. The genetic analyses showed two mutations: a stop mutation in exon 11/20 (NM_004100.4:c.940G>T) of the EYA4 gene and a missense mutation in exon 6 (NM_000117.2:c.548C>G) of the EMD gene. Discussion and conclusion: The in silico predictions described the EYA4 variant as likely pathogenic and the EMD variant as a variant of uncertain significance (VUS). Moreover, an ancestry analysis was performed using 46 Ancestry Informative Insertion/Deletion Markers (AIM-InDels), and the ancestral composition of subject A was 46% African, 26.1% European, and 27.9% American Indian ancestry, whereas the ancestral composition of subject B was 41.3% African, 38.2% European, and 20.5% American Indian ancestry. The present case report describes two Ecuadorian siblings with a mainly African ancestral component, muscular dystrophy, and deafness phenotypes. Moreover, using next-generation sequencing (NGS), a mutation in the EMD and a novel mutation in EYA4 genes possibly associated with the subjects' phenotype were identified and discussed.

Genomic analysis of a novel pathogenic variant in the gene LMNA associated with cardiac laminopathies found in Ecuadorian siblings: A case report.

Introduction: Cardiac laminopathies are caused by mutations in the LMNA gene and include a wide range of clinical manifestations involving electrical and mechanical changes in cardiomyocytes. In Ecuador, cardiovascular diseases were the primary cause of death in 2019, accounting for 26.5% of total deaths. Cardiac laminopathy-associated mutations involve genes coding for structural proteins with functions related to heart development and physiology. Family description: Two Ecuadorian siblings, self-identified as mestizos, were diagnosed with cardiac laminopathies and suffered embolic strokes. Moreover, by performing Next-Generation Sequencing, a pathogenic variant (NM_170707.3:c.1526del) was found in the gene LMNA. Discussion and conclusion: Currently, genetic tests are an essential step for disease genetic counseling, including cardiovascular disease diagnosis. Identification of a genetic cause that may explain the risk of cardiac laminopathies in a family can help the post-test counseling and recommendations from the cardiologist. In the present report, a pathogenic variant ((NM_170707.3:c.1526del) has been identified in two Ecuadorian siblings with cardiac laminopathies. The LMNA gene codes for A-type laminar proteins that are associated with gene transcription regulation. Mutations in the LMNA gene cause laminopathies, disorders with diverse phenotypic manifestations. Moreover, understanding the molecular biology of the disease-causing mutations is essential in deciding the correct type of treatment.